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CYP11B1和CYP11B2基因多态性与醛固酮瘤发病风险的相关性
2019年
目的探讨11-β羟化酶(CYP11B1)、醛固酮合酶(CYP11B2)基因多态性与醛固酮瘤(APA)发病风险的相关性。方法采用实时荧光定量聚合酶链式反应(real-time PCR)TaqMan-MGB探针法检测80例醛固酮瘤患者(APA组)和101例体检健康者(对照组)外周血中CYP11B1基因rs5301、rs6471570及CYP11B2基因rs3802228、rs3802230、rs4545、rs4546、rs6433单核苷酸多态性(SNP)位点,应用SNPassoc1.9-2和Haplo Stats2.17.0软件分析CYP11B2和CYP11B1基因型和单体型与APA发病风险的相关性。结果APA组CYP11B1基因rs5301位点的A等位基因和CYP11B2基因rs3802228位点的A等位基因、rs6433位点的G等位基因频率均高于对照组(P均<0.05);将性别、年龄及BMI校正后,APA组CYP11B2基因rs4545位点AG基因型频率低于对照组(P<0.05)。单体型分析发现,APA组GAACAAC、GCGAAGT频率低于对照组(P=0.012,OR=0.73,95%CI为0.57~0.93;P=0.012,OR=0.81,95%CI为0.69~0.95)。结论CYP11B1和CYP11B2基因多态性与APA发病相关。其中,CYP11B2基因多态性位点rs4545与APA人群有关,CYP11B2基因和CYP11B1基因组成的单体型GAACAAC、GCGAAGT与APA发病风险呈负相关。
黄若辉康欢邹晓峰张国玺王保军欧阳金芝马鑫张旭曾庆明曾晓鹏
关键词:醛固酮合酶基因多态性醛固酮瘤
醛固酮合酶基因和11-β羟化酶基因多态性及其单体型与醛固酮瘤发病风险的关系被引量:2
2014年
目的探讨醛固酮合酶基因(CYP11B2)和11-β羟化酶基因(CYP11B1)多态性及其单体型与醛固酮瘤发病风险的关系。方法提取81例醛固酮瘤患者和103例对照人群外周血DNA,应用2个独立聚合酶链反应(PCa)和TaqMan探针技术对CYP11B2和CYP11B1基因的7个多态性位点(rs6387、rs6410、rs3097、rs4539、intron2转位、rs1799998、rs13268025)进行基因分型,采用Logistic回归模型分析不同等位基因、基因型和单体型与醛固酮瘤发病风险的相关性。结果intron2转位多态性位点C等位基因在病例组中的分布频率(25.3%)高于对照组(15.0%),携带C等位基因的个体较携带W等位基因的个体发生醛固酮瘤的风险增加了1.04倍(P〈0.01)。rs13268025位点中携带C等位基因的个体较携带T等位基因的个体发生醛固酮瘤的风险增加了0.91倍(P〈0.05)。7个多态性位点间存在着不同程度的连锁不平衡。单体型分析示AGGAWTF为最常见的单体型,单体型GAGAWTF是AGGAWTF发病风险的4.43倍(P〈0.01)。结论CYP11B2和CYP11B1基因多态性与醛固酮瘤发病风险明显相关,intron2转位多态性位点的C等位基因、rs13268025位点的C等位基因、单体型GAGAWTT是醛固酮瘤发病的危险因素。
王保军陈路遥李新涛马鑫杨素霞欧阳金芝张旭
关键词:醛固酮瘤醛固酮合酶基因多态性单体型
Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism
2016年
Background: Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. Methods: This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17 30 years) and 135 healthy controls after matching tbr gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone. ACTH, and cortisol and biochemical tests. Results: Higher basal serum ACTH levels (8.25 ±3.78 pmol/L vs. 6.97 ±2.81 pmol/L) and lower cortisol levels (366.70 ±142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed ill male IHH patients than healthy subjects (all P 〈 0.05). IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P 〈 0.05). Basal serum ACTH (9.91 ±4.98 pmol/L vs. 7.60 ±2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ±925.8 μg/L vs. 1417.1 ±498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P 〈 0.05). We also found that basal serum ACTH levels were positively correlated with NAFLD (r = 0.289, P 〈 0.05) and triglyceride levels (r - 0.268, P 〈 0.05) in male IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. Conclusions: The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels
Wen-Bo WangFei SheLi-Fang XieWen-Hua YanJin-Zhi OuyangBao-An WangHang-Yun MaLi ZangYi-Ming Mu
原发性醛固酮增多症遗传学研究进展被引量:2
2015年
原发性醛固酮增多症(primary aldosteronism,PA)是一种常见的、可治愈的继发性高血压的原因之一,主要由醛固酮瘤(aldosterone-producing adenoma,APA)或特发性醛固酮增多症(idiopathic hyperaldosteronism,IHA)引起,只有小部分的PA是家族性醛固酮增多症(familial hyperaldosteronism,FH)。基因组学技术的发展,使得人们逐步阐明了与APA、IHA和FH发生有关的部分异常基因。本文主要描述了与PA有关的异常基因,以期为PA分型诊断和继发性高血压的治疗提供新的方向。
谢利芳欧阳金芝母义明
关键词:原发性醛固酮增多症醛固酮瘤钾离子通道体细胞突变
Gene Expression Profile of Persistent Postoperative Hypertension Patients with Aldosterone-producing Adenomas被引量:5
2015年
Background:Hypertension often persists after adrenalectomy for primary aldosteronism (PA).Many studies have analyzed the outcomes of adrenalectomy for aldosterone-producing adenomas (APA) to identify predictive factors for persistent hypertension.However,differentially expressed genes in persistent postoperative hypertension remain unknown.Our aim was to describe gene expression profile of persistent postoperative hypertension patients with APA.Methods:In this study,we described and compared gene expression profiles in persistent postoperative hypertension and postoperative normotension in Chinese patients with APA using microarray analysis.Confirmation was performed with quantitative real time-polymerase chain reaction analysis.Bioinformatic analysis (gene ontology analysis,pathway analysis and network analysis) was used for further research.Results:Microarray analysis identified a total of 99 differentially expressed genes,including 18 up-regulated and 81 down-regulated genes.Among the dysregulated genes were fat atypical cadherin 1 as well as fatty acid binding protein 4 and other genes that have not been previously studied in persistent postoperative hypertension with APA.Bioinformatics analysis indicated that differentially expressed genes were associated with lipid metabolic process,metal ion binding,and cell differentiation.Pathway analysis determined that five pathways corresponded to the dysregulated transcripts.The mRNAs-ncRNAs co-expression network was composed of 49 network nodes and 72 connections between 18 coding genes and 31 noncoding genes.Conclusions:This study revealed differentially expressed genes in persistent postoperative hypertension with APA and provided a resource of candidate genes for exploration of possible drug targets and prognostic markers.
Li-Fang XieJin-Zhi OuyangAn-Ping WangWen-Bo WangXin-Tao LiBao-Jun WangYi-Ming Mu
关键词:HYPERTENSIONMICROARRAYPATHWAY
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